Patent TW-401407-B (TW)
Title: Delta 6,7-taxols antineoplastic use and pharmaceutical compositions containing them
Inventor: KELLY ROBERT C
IPC: A61P35/00
Filed: 1994-06-09
Granted: 2000-08-11
Abstract: A compound of the formula I: wherein: R1 is selected from the group consisting of -CH3, -C6H5 or phenyl substituted with one, 2 or 3 C1-C4 alkyl, C1-C3 alkoxy, halo, C1-C3 alkylthio, trifluoromethyl, C2-C6 dialkylamino, hydroxy or nitro, -2-furyl, 2-thienyl, 1-naphthyl, 2-naphthyl or 3,4-methylenedioxyphenyl; R2 is selected from the group consisting of -H, -NHC(O)H, -NHC(O)C1-C10alkyl-NHC(O)phenyl, -NHC(O)phenyl substituted with one, 2 or 3 C1-C4 alkyl, C1-C3 alkoxy, halo, C1-C3 alkylthio, trifluoromethyl, C2-C6 dialkylamino, hydroxy or nitro, -NHC(O)C(CH3)-CHCH3, -NHC(O)OC(CH3)3, -NHC(O)OCH2phenyl, -NH2, -NHSO2-4-methyl-phenyl, -NHC(O)(CH2)3COOH, -NHC(O)-4-(SO3H)phenyl, -OH, -NHC(O)-1-adamantyl, -NHC(O)O-3-tetrahydrofuranyl, -NHC(O)O-4-tetrahydropyranyl, -NHC(O)CH2C(CH3)3, NHC(O)C(CH3)3, -NHC(O)OC1-C10alkyl, -NHC(O)NHC1-C10alkyl, -NHC(O)NHPh, -NHC(O)NHPh substituted with one, 2 or 3 C1-C4 alkyl, C1-C3 alkoxy, halo, C1-C3 alkylthio, trifluoromethyl, C2-C6 dialkylamino, or nitro, -NHC(O)C3-C8cycloalkyl, -NHC(O)C(CH2CH3)2CH3, -NHC(O)C(CH3)2CH2CI, -NHC(O)C(CH3)2CH2CH3, phthalimido, -NHC(O)-1-phenyl-1-cyclophenyl, -NHC(O)-1-methyl-1-cyclohexyl, -NHC(S)NHC(CH3)3, or -NHC(O)NHC(CH3)3; R3 is selected from the group consisting of -H, -NHC(O)phenyl or -NHC(O)OC(CH3)3, with the overall proviso that one of R2 and R3 is -H but R2 and R3 are not both -H; R4 is -H or selected form the group consisting of -OH, -OAc (-OC(O)CH3), -OC(O)OCH2C(CI)3, -OCOCH2CH2NH3<+>HCOO<->, -NHC(O)phenyl, -NHC(O)OC(CH3)3, -OCOCH2CH2COOH and pharmaceutically acceptable salts thereof, -OCO(CH2)3COOH and pharmaceutically acceptable salts thereof, and -OC(O)-Z-C(O)-R' [where Z is ethylene(-CH2CH2-), phenylene (-CH2CH2CH2-), -CH=CH-, 1,2-cyclohexane or 1,2-phenylene, R' is -OH, -OH base, -HR'2R'3, -OR'3, -SR'3, -OCH2C(O)NR'4R'5 where R'2 is -H or -CH3, R'3 is -(CH2)nNR'6R'7 or (CH2)nN<+>R'6R'7R'8 X<-> where n is 1-3, R'4 is -H or-C1-C4alkyl, R'5 is -H, -C1-C4alkyl, benzyl, hydroxyethyl, -CH2CO2H or dimethylaminoethyl, R'6 and R'7 are -CH3, -CH2-CH3, benzyl or R'6 and R'7 together with the nitrogen of NR'6R'7 from a pyrrolidino, piperidino, morpholino, or N-methylpiperizino group; R'8 is -CH3, -CH2CH3 or benzyl, X<-> is halide, and base is NH3, (HOC2H4)3N, N(CH3)3, CH3N(C2H4)2NH2, NH2(CH2)6NH2, N-methylglucamine, NaOH or KOH], -OC(O)(CH2)nNR<2>R<3> [where n is 1-3, R<2> is -H or -C1-C3alkyl and R<3> is -H or -C1-C3alkyl], -OC(O)CH(R"")NH2 [where R"" is selected from the group consisting of -H, -CH3, -CH2CH(CH3)2, -CH(CH3)CH2CH3, -CH(CH3)2, -CH2phenyl, -(CH2)4NH2, -CH2CH2COOH, -(CH2)3NHC(=NH)NH2], the residue of the amino acid proline, -OC(O)CH=CH2, -C(O)CH2CH2C(O)NHCH2CH2SO3<->Y<+>, -OC(O)CH2CH2C(O)NHCH2CH2CH2SO3<->Y<+> wherein Y<+> is Na<+> or N<+>(Bu)4, -OC(O)CH2CH2C(O)OCH2CH2OH; R5 is -H or -OH, with the overall proviso that when R5 is -OH, R4 is -H and with the further proviso that when R5 is -H, R4 is other than -H; R10 is -H or -C(O)CH3; R17 is -H, -C(O)C5H6, -C(O)phenyl substituted with one, 2 or 3 azido, cyano, methoxy, or halo; and pharmaceutically acceptable salts thereof when the compound contains either an acidic or basic functional group with the overall proviso that when R3 and R5 are -H and R17 is -C(O)C6H5, either R1 is selected fom the group consisting of phenyl substituted with one, 2 or 3 C1-C3 alkylhtio, C2-C6 dialkylamino, hydroxy or nitro, or 3,4-methylenedioxyphenyl; or R2 is selected from the group consisting of -NHC(O)H, -NHC(O)phenyl substituted with one, 2 or 3 C1-C3 alkylthio, C2-C6 dialkylamino, hydroxy or nitro, -NH2, -NHSO2, -NHSO2-4-methylphenyl, -NHC(O)(CH2)3COOH, -NHC(O)-4-(SO3H)phenyl, -OH, -NHC(O)-1-adamantyl, -NHC(O)O-3-tetrahydrofuranyl, -NHC(O)O-4-tetrahydropyranyl, -NHC(O)NHC1-C10alkyl, -NHC(O)NHPh, -NHC(O)NHPh substituted with one, 2 or 3 C1-C4 alkyl, C1-C3 alkoxy, halo, C1-C3 alkylthio, trifluoromethyl, C2-C6 dialkylamino, or nitro, -NHC(O)C(CH3)2CH2C1, phthalimido, -NHC(O)-1-phenyl-1-cyclopentyl, -NHC(O)-1-methyl-1-cyclohexyl, -NHC(S)NHC(CH3) or -NHC(O)NHC(CH3)3.